J. Am. Chem. Soc. 1996, 118, 897-898
Stereocontrolled Oxidative Addition of Zerovalent Molybdenum to Enantiomerically Pure Allylic Acetates with Either Inversion or Retention at the Stereogenic Center
897
Scheme 1
Yancey D. Ward,1 Lawrence A. Villanueva, Gary D. Allred, and Lanny S. Liebeskind* Sanford S. Atwood Chemistry Center, Emory UniVersity 1515 Pierce DriVe, Atlanta, Georgia 30322 ReceiVed August 25, 1995 In both the catalytic and stoichiometric manifold, allylic substitutions catalyzed by transition metal complexes have contributed significantly to the library of transformations available to the synthetic organic chemist. Palladium and molybdenum appear prominently in synthetically useful, metalmediated allylic substitutions, the former in catalytic2-8 and the latter in both catalytic and stoichiometric modes.9-24 Essential to the use of these processes in synthesis is control of (1) the stereochemistry of the oxidative addition of the metal to the allylic substrate and (2) the regiochemistry and stereochemistry of the nucleophilic attack. Most palladium-catalyzed reactions of allylic substrates with stabilized enolates proceed with overall retention of configuration, an outcome dictated by an anti oxidative addition and an anti nucleophilic attack on an η3allyl. Though not common, formation of an (η3-allyl)palladium via syn oxidative addition has been demonstrated for allylic substrates bearing various leaving groups (Ph2PCH2CO2, Cl, OCOCF3).25-27 Molybdenum-catalyzed allylic alkylations occur with net retention of configuration, suggesting a doubleinversion mechanism similar to the palladium case. However, Kocˇovsky´ and co-workers have very recently offered strong evidence implicating a double-retention pathway28 which bears upon earlier observations by Trost and co-workers that Mo(1) Current address: Boehringer Ingelheim Pharm., Inc., 900 Ridgebury Rd., P. O. Box 368, Ridgefield, CT 06877. (2) Trost, B. M. Angew. Chem., Int. Ed. Engl. 1995, 34, 259. (3) Trost, B. M. Pure Appl. Chem. 1992, 64, 315. (4) Backvall, J. E. Pure Appl. Chem. 1992, 64, 429. (5) Takahara, J. P.; Masuyama, Y.; Kurusu, Y. J. Am. Chem. Soc. 1992, 114, 2577. (6) Larsson, E. M.; Akermark, B. Tetrahedron Lett. 1993, 34, 2523. (7) Tsuji, J. Pure Appl. Chem. 1981, 53, 2371. (8) Consiglio, G.; Waymouth, R. M. Chem. ReV. 1989, 89, 257. (9) Trost, B.; Merlic, C. J. Am. Chem. Soc. 1990, 112, 9590. (10) Trost, B.; Lautens, M. J. Am. Chem. Soc. 1987, 109, 1469. (11) Faller, J. W.; Ma, Y. N. Organometallics 1993, 12, 1927. (12) Faller, J. W.; Nguyen, J. T.; Ellis, W.; Mazzieri, M. R. Organometallics 1993, 12, 1434. (13) Pearson, A. J.; Mallik, S.; Pinkerton, A. A.; Adams, J. P.; Zheng, S. J. Org. Chem. 1992, 57, 2910. (14) Pearson, A. J.; Mallik, S.; Mortezaei, R.; Perry, M. W. D.; Shively, R. J., Jr.; Youngs, W. J. J. Am. Chem. Soc. 1990, 112, 8034. (15) Yu, R., H.; McCallum, J. S.; Liebeskind, L. S. Organometallics 1994, 13, 1476. (16) Rubio, A.; Liebeskind, L. S. J. Am. Chem. Soc. 1993, 115, 891. (17) Liebeskind, L. S.; Bombrun, A. J. Am. Chem. Soc. 1991, 113, 8736. (18) Hansson, S.; Miller, J. F.; Liebeskind, L. S. J. Am. Chem. Soc. 1990, 112, 9660. (19) Su, G. M.; Lee, G. H.; Peng, S. M.; Liu, R. S. J. Chem. Soc., Chem. Commun. 1992, 215. (20) Lin, S. H.; Peng, S. M.; Liu, R. S. J. Chem. Soc., Chem. Commun. 1992, 615. (21) Yang, G. M.; Su, G. M.; Liu, R. S. Organometallics 1992, 11, 3444. (22) Lin, S.-H.; Yang, Y.-J.; Liu, R.-S. J. Chem. Soc., Chem. Commun. 1991, 1004. (23) Yang, G.-M.; Lee, G.-H.; Peng, S.-M.; Liu, R.-S. Organometallics 1991, 10, 2531. (24) Vong, W.-J.; Peng, S.-M.; Lin, S.-H.; Lin, W.-J.; Liu, R.-S. J. Am. Chem. Soc. 1991, 113, 573. (25) Vitagliano, A.; A° kermark, B.; Hansson, S. Organometallics 1991, 10, 2592. (26) Stary´, I.; Zajı´cˇek, J.; Kocˇovsky´, P. Tetrahedron 1992, 48, 7229. (27) Kurosawa, H.; Kajimaru, H.; Ogoshi, S.; Yoneda, H.; Miki, K.; Kasai, N.; Murai, S.; Ikeda, I. J. Am. Chem. Soc. 1992, 114, 8417. (28) Dvor´a´k, D.; Stary´, I.; Kocˇovsky´, P. J. Am. Chem. Soc. 1995, 117, 6130.
0002-7863/96/1518-0897$12.00/0
(CO)6-catalyzed substitutions of allylic acetates in toluene occur with overall retention of stereochemistry.9,10 Oxidative addition with retention of stereochemistry has been unambiguously demonstrated in the stoichiometric reaction of Mo(CO)3(CH3CN)3 with both acyclic29 and cyclic16 allylic acetates. During a previous study, the enantiomerically pure pyranone 1, derived from D-glucose,30 produced the (π-allyl)molybdenum complex 4 with retention of allylic acetate stereochemistry (Scheme 1).16 Surprisingly, the related allylic acetates 2 and 3(S) derived from D-galactose31 and D-arabinose,31 respectively, failed to give analogous π-allyl complexes under standard conditions. However, using a recently described protocol32 for the preparation of complexes based on the hydridotris(1pyrazolyl)borate ligand33,34 (Tp), this limitation was overcome and a practical construction of enantiomerically enriched (πallyl)molybdenum complexes derived from D-glucose, D-galactose, and D- and L-arabinose was achieved. During these and ancillary studies a delicately balanced yet synthetically useful competition between retention and inversion pathways for the oxidative addition was revealed. Treatment of the dihydropyranone 1 with 1.0 equiv of (DMF)3Mo(CO)335 in CH2Cl2 at room temperature followed by addition of potassium hydridotris(pyrazolyl)borate (K+Tp-) provided complex 5 in 91% yield with complete retention of configuration. Under identical reaction conditions the diastereomeric dihydropyranone 2 gave in 82% yield a 12:1 mixture of the complexes 5 and 6, the result of a highly selective inVersion of configuration. Diastereomer 6 was independently prepared in modest yield by the addition of dihydropyranone 2 to a solution of (toluene)Mo(CO)336 in CH2Cl2 at 25 °C followed by the addition of K+Tp-. Under these conditions, the mode of oxidative addition switched and proceeded with complete retention of stereochemistry. The relative stereochemical relationship of the TpMo(CO)2 fragment and the acetoxymethyl group in complexes 5 and 6 was deduced by the conversion of 5 into (2S,6R)-2-(acetoxymethyl)-6-methyltetrahydropyran16 (see supporting information). These observations underscored the ease with which the oxidative addition of zerovalent molybdenum to an allylic acetate can proceed through either a retention or an inversion mechanism in response to the Mo(0) source as well as to steric constraints imposed by the substrate. In that light, conversion of the sterically unbiased dihydropyranone 3(S) into its corre(29) Faller, J. W.; Linebarrier, D. Organometallics 1988, 7, 1670. (30) Jarglis, P.; Lichtenthaler, F. W. Tetrahedron Lett. 1982, 23, 3781. (31) Lichtenthaler, R. W.; Ro¨nninger, S.; Jarglis, P. Liebigs Ann. Chem. 1989, 1153. (32) Ward, Y. D.; Villanueva, L. A.; Allred, G. D.; Payne, S. C.; Semones, M. A.; Liebeskind, L. S. Organometallics 1995, 14, 4132. (33) Trofimenko, S. Chem. ReV. 1993, 93, 943. (34) Trofimenko, S. Acc. Chem. Res. 1971, 4, 17. (35) Pasquali, M.; Leoni, P.; Sabatino, P.; Braga, D. Gazz. Chim. Ital. 1992, 122, 275. (36) Nesmeyanov, A. N.; Krivykh, V. V.; Kaganovich, V. S.; Rybinskaya, M. I. J. Organomet. Chem. 1975, 102, 185.
© 1996 American Chemical Society
898 J. Am. Chem. Soc., Vol. 118, No. 4, 1996 sponding (π-allyl)molybdenum complex proved instructive. Addition of 3(S) to a CH2Cl2 solution of (DMF)3Mo(CO)3 at 22 °C followed 2 h later by the addition of K+Tp- provided a 34:66 mixture of enantiomers corresponding to retention product 7 and inversion product 8, respectively, in 93% isolated yield. The selectivity for the inVersion enantiomer 8 was improved either by lowering the reaction temperature or by using 2 equiv of (DMF)3Mo(CO)3. Addition of 3(S) to a CH2Cl2 solution of 2 equiv of (DMF)3Mo(CO)3 at -40 °C followed by the addition of K+Tp- provided the inVersion enantiomer 8 in 57% yield and 84% ee. Dramatically, a simple solvent change from CH2Cl2 to THF produced an excess of the retention enantiomer 7 (86% yield, 88% ee), which was also obtained in excellent yield and enantiomeric excess (86% yield and 94% ee) by adding a solution of (DMF)3Mo(CO)3 in CH2Cl2 dropwise over a 45 min period to the allylic acetate 3(S) (inverse addition). The enantiopurities were determined by chiral shift reagent analysis of the 1H NMR spectra using Eu(hfc)3; the assignment of 7 and 8 is described below. Consistent with the double-retention pathway for molybdenumcatalyzed allylic substitutions,9,10,28 dihydropyranone 3(S) reacted with Mo(CO)6 in refluxing toluene followed by metathesis with K+Tp- to produce 7 with high enantiomeric excess (>90%), although the chemical yields were low and variable (18-40%). However, using (toluene)Mo(CO)336 in CH2Cl2, the oxidative addition proceeded at room temperature and gave the retention product 7 in good isolated yield (60-70%) with excellent ee’s (>95%). Unlike reactions with (DMF)3Mo(CO)3, the enantiomeric excess of the product generated from (toluene)Mo(CO)3 was not concentration dependent: the addition of 5.8 g of 3(S) to 9.1 g of (toluene)Mo(CO)3 in 30 mL of CH2Cl2 gave 10.4 g of 7 in 67% yield and 96% ee. The enantiomer 8 is available from 3(S) and (DMF)3Mo(CO)3, as described above, in 57% yield and 84% ee, or more conveniently from dihydropyranone 3(R) (prepared from L-arabinose31) in 63% yield and 98% ee. The enantiopurities of 7 and 8 were determined by HPLC analysis using a Chiralpak AD column. The absolute stereochemistry of the retention product, 7, was established through X-ray crystallography37 and by conversion of 7 through standard functionalization to (2S,6S)-(cis-6-methyltetrahydropyran-2-yl)acetic acid methyl ester38 (see supporting information). The experiments outlined above suggested that the retention pathway was favored at low effective concentration of (DMF)3Mo(CO)3 relative to the allylic acetate (dilute solution, e1 equiv of Mo(0), slow addition of Mo(0) to allylic acetate), or more simply by the use of (toluene)Mo(CO)3. The inversion pathway predominated at high effective concentration of (DMF)3Mo(CO)3 relative to the allylic acetate (concentrated solution, >1 equiv of Mo(0), addition of the allylic acetate to Mo(0)) and at low temperature. These observations suggest that the mechanistic pathways leading to the retention and inversion products differ in the order of the metal in the ratedetermining steps and are consistent with the rationale shown in Scheme 2.39 The pathways diverge from the intermediate, 9, where a 16-electron Mo(0) fragment is coordinated to the allylic acetate leaving group. At low Mo(0) concentration, further ligand loss from the Mo(0) fragment of 9 could lead to the chelated intermediate 10, which would undergo internal redox providing the retention oxidative addition product. Since (37) Crystal data for 7: orange/red prisms (0.22 × 0.33 × 0.41) from CH2Cl2 (C16H15BMoN6O4, FW ) 462.09, orthorhombic, P212121, a ) 12.980(4) Å, b ) 13.604(3) Å, c ) 20.067(5) Å, V ) 3544(2) Å3, λ(Mo KR) ) 0.710 73 Å, Dc ) 1.516 g/cm3, Z ) 6, T ) 173 K, F(000) ) 1624, µ ) 6.81 cm-1). Of the 13 418 data (including Friedel pairs) collected, 4336 were considered observed (F > 4.0 σ(F)). The structure was solved by Patterson methods and refinement carried out using SHELXTL (1994). The absolute stereochemistry was determined by collecting Friedel pairs and inverting the structure to give the absolute structure parameter of 0.04(12). Full-matrix least-squares refinement on F2 resulted in a final Rindex (observed data) of 5.46%, a goodness of fit of 1.073, and a data-to-parameter ratio of 9:1. (38) Seebach, D.; Pohmakotr, M. HelV. Chim. Acta 1979, 62, 843.
Communications to the Editor Scheme 2
this path requires facile and multiple ligand dissociation from the Mo(0) species, it should be favored by Mo(0) species capable of low coordination numbers (i.e., loss of toluene from (toluene)Mo(CO)3). At high Mo(0) concentrations, intermediate 9 could competitively combine with another 16-electron Mo(0) fragment leading to the doubly coordinated species 11. Steric effects would dictate coordination of the second Mo(0) trans to the allylic acetate group and lead to the inversion oxidative addition product. At low temperature, entropic factors (T∆S) should increase the concentration of the doubly coordinated species 11 and lead to an increase in the inversion product, as observed. Through the proper choice of reaction conditions a single enantiomer of the allylic acetates investigated in this study can be transformed by either a retention or inversion process into a (π-allyl)molybdenum complex in good yield and with high enantiopurity. The facility with which the mechanism of oxidative addition changes from retention to inversion clearly suggests that observations of overall retention of stereochemistry in molybdenum-catalyzed allylic substitutions of sterically unbiased substrates can be accounted for by either an inversioninversion or a retention-retention pathway. These results prescribe the use of caution in predicting the stereochemical outcome of molybdenum-catalyzed allylic substitutions. The pyranose-derived (π-allyl)molybdenum complexes described in this study are readily available on large scale in high yield and high enantiopurity from inexpensive materials. The use of these complexes in enantiocontrolled organic synthesis will be described in forthcoming papers. Acknowledgment. This investigation was supported by Grant No. GM43107, awarded by the National Institute of General Medical Sciences, DHHS. We acknowledge the use of a VG 70-S mass spectrometer purchased through funding from the National Institutes of Health, S10-RR-02478, and a 300 and a 360 MHz NMR purchased through funding from the National Science Foundation, NSF CHE85-16614 and NSF CHE-8206103, respectively. We thank Professor Pavel Kocˇovsky´ (University of Leicester, U.K.) for sharing his results with us prior to publication and for his valuable comments. L.A.V. acknowledges funding from the NIH through a minority supplement to Grant No. GM43107. Supporting Information Available: Complete description of the synthesis and characterization of all compounds in the manuscript and a listing of bond lengths and angles, non-hydrogen thermal parameters, and hydrogen fixed positional and final thermal parameters for the crystal structure determination of compound 7 (27 pages). This material is contained in many libraries on microfiche, immediately follows this article in the microfilm version of the journal, can be ordered from the ACS, and can be downloaded from the Internet; see any current masthead page for ordering information and Internet access instructions. JA952938B (39) One referee suggested that dihydropyranones 3(S) and 3(R), while not sterically biased, are conformationally biased. A conformational bias would be mechanistically significant only if the more abundant half-chair (pseudoequatorial OAc) and the less abundant half-chair (pseudoaxial OAc) each react selectively under different reaction conditions. To account for the observed oxidative addition stereoselectivities, oxidative addition at low Mo(0) concentration could proceed selectively syn to the pseudoaxial allylic acetate, in which case at high effective Mo(0) concentration oxidative addition must proceed anti to the pseudoequatorial OAc group, possibly through a molybdenum aggregate.
